Distinct Clinical Differences Between HLA-Cw0602 Positive and Negative Psoriasis Patients – An Analysis of 1019 HLA-C- and HLA-B-Typed Patients

• Published in: Journal of investigative dermatology Vol. 126; no. 4; pp. 740 - 745
• Main Authors: Gudjonsson, Johann E., Karason, Ari, Hjaltey Runarsdottir, E., Antonsdottir, Arna A., Hauksson, Valdimar B., Jónsson, Hjörtur H., Gulcher, Jeff, Stefansson, Kari, Valdimarsson, Helgi
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.04.2006; Nature Publishing; Elsevier Limited
• Subjects: Adolescent; Adult; Biological and medical sciences; Chromosomes, Human, Pair 6 - genetics; Chronic Disease; Dermatology; Female; HLA-B Antigens - analysis; HLA-C Antigens - analysis; HLA-C Antigens - genetics; Humans; Male; Medical sciences; Pregnancy; Psoriasis - diagnosis; Psoriasis - genetics; Psoriasis - immunology; Psoriasis. Parapsoriasis. Lichen; Severity of Illness Index; Human; HLA-System; Skin disease; Psoriasis; Dermatology; Major histocompatibility system; HLA-C-Locus; Class I histocompatibility antigen; Comparative study; HLA-B-Locus
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/sj.jid.5700118

A major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10−10), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined.